Core C - Meenhard Herlyn This Cell Biology Core has major resources available that are provided to the program project investigators, including melanocytes, keratinocytes, fibroblasts, endothelial cells, bone marrow-derived mesenchymal stem cells, melanoma cells, monoclonal antibodies to melanoma-associated antigens, adenoviral and lentiviral vectors for growth factors, adhesion molecules, and oncogenes. Three-dimensional cultures of normal human skin (skin equivalents, organotypic cultures of skin) with a 'dermis'of fibroblasts embedded in collagen and an 'epidermis'of melanocytes/melanoma cells and keratinocytes are generated and provided to the program investigators. This three-dimensional model is superior to two- dimensional culture because it mimics the in vivo context for the melanocytes/melanoma cells. For screening studies, the Core is providing a spheroid culture model that allows investigations on melanoma cells intimately interacting with stromal cells. The Core provides to program members orthotopic in vivo models of melanoma growth. Due to the different architectures between mouse and human skin, melanomas, including xenografted cells, cannot be grown in the natural murine skin environment. Instead, the Core will first graft human skin onto immunodeficient mice. When the skin has healed, we will inject human melanoma cells intradermally, where growth and invasion occurs in the same way as in patients'lesions. The Core is also providing the subcutaneous melanoma growth model for standard experiments. Besides providing resources to the other projects, the Core will test compounds developed in Projects 3 and 4 and initially selected in Project 1. The responsibility of the Core is in testing expanded number of cell lines, in quality control testing of compounds through the different biological assays and through Western blotting. The Core also trains investigators of the Program in all tumor biological assays. Overall, this Core will provide efficient and high quality service to all interested laboratories within this Program Project.